title: At the Bedside: Innate immunity as an immunotherapy tool for hematological malignancies.
abstract: The identification of an anti-tumor effect displayed by cells of innate immunity has opened new scenarios, not only in the field of allo-HSCT but also for nontransplanted patients with hematological malignancies or solid tumors. Donor-derived NK cells have been shown to contribute to the eradication of malignant cells after allo-HSCT, when recipients lack ligands for their inhibitory receptors. These alloreactive donor NK cells can also kill recipient APCs and CTLs, thus preventing the occurrence of GvHD and graft rejection. The role of activating receptors on the capacity of NK cells to kill leukemia targets has become evident in the last years. The adoptive infusion of ex vivo-activated NK cells has been investigated recently in Phase I/II trials on patients with hematological malignancies and solid tumors, with promising results. γδ T lymphocytes are also able to display anti-tumor activity-this providing the biological rationale for Phase I/II trials in lymphoproliferative disorders and solid tumors. Aminobisphosphonates are clinically available compounds able to boost γδ T cell function. As γδ T cells do not cause GvHD, they could also be transduced with tumor-associated chimeric antigen receptors and safely infused in allo-HSCT recipients. Basic aspects of innate immunity relevant to the field will be covered by a companion review article.
authors.affiliation: 1.Piazza Sant'Onofrio 4, 00165 Rome, Italy. franco.locatelli@opbg.net.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Pietro
authors.initials: P
authors.lastname: Merli
authors.forename: Sergio
authors.initials: S
authors.lastname: Rutella
mesh_terms: D019264:Adoptive Transfer; D000938:Antigen-Presenting Cells / Q000276:immunology; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation*; D017710:Lymphocyte Transfusion
keywords: Haploidentical hematopoietic stem cell transplantation; NK cells; graft-versus-host disease; graft-versus-leukemia effect; γ-δ T cells